Background: Recent studies have suggested that dipeptidyl peptidase-4 (DPP4) may facilitate SARS-CoV-2 entry into target cells, and thus DPP4 inhibitors (DPP4i) could have protective effects on COVID-19. Given the high fatality rate of COVID-19 patients with diabetes, there is an urgent need to understand the effect DPP4i may have on COVID-19.
Objectives: To determine whether use of DPP4i reduces the risk of adverse COVID-19 related outcomes among patients with type 2 diabetes (T2D).
Methods: We conducted a nationwide cohort study using Korea’s healthcare database linked with the Disease Control and Prevention Agency database, between Jan 1, 2017 and May 15, 2020. We included patients aged ≥18 years, tested positive for COVID-19, previously diagnosed with T2D, and had ≥1 antidiabetic prescription within the 180 days prior to COVID 19 diagnosis. Patients classified into two discrete exposure groups: users of DPP4i, and users of other second- or third-line antidiabetics (reference group). The primary and secondary outcomes were all-cause mortality and severe manifestations of COVID-19 (a composite endpoint of an intensive care unit admission and use of mechanical ventilation or extracorporeal membrane oxygenation), respectively. Cox proportional hazards model was used to estimate hazard ratio (HR) with 95% confidence interval (CI), adjusted for potential confounding.
Results: Of 586 patients in our study cohort, there were 47 deaths among 453 users of DPP4i (incidence rate 1.73 per 1,000 person-days), and 22 deaths among 133 users of other second- or third-line antidiabetics (3.18 per 1,000 person-days). The unadjusted survival curves demonstrated a significant lower probability of all-cause mortality (p=0.044) and severe manifestations (p=0.008) among DPP4i users. In the adjusted Cox model, DPP4i use was insignificantly associated with all-cause mortality (HR 0.74, 95% CI 0.43-1.26) and severe manifestations (HR 0.83, 95% CI 0.45-1.53), compared to the reference group.
Conclusions: In this nationwide cohort study, we found no significant association between the use of DPP4i and adverse COVID-19 related outcomes among patients with COVID-19 and T2D. However, although our estimates had wide 95% CIs, a reduction of mortality and severe manifestations was observed in DPP4i users, suggesting clinical relevance of potential benefit associated with DPP4i.